[Requirements and performance profile of the Paediatric Radiation Oncology Working Group (APRO): evaluation of the present situation and description of future developments]. / Anforderungen und Leistungsprofile der Arbeitsgemeinschaft Pädiatrische Radioonkologie (APRO): Eine Bestandsaufnahme und Darstellung zukünftiger Entwicklungen.

BACKGROUND: Radiation therapy is an integral component in the management of childhood malignancies and undergoes a continuous process of optimization within the prospective trials of the GPOH. At present there are approximately 20 active protocols, some specifying radio-oncological study questions, in which about 500 to 600 children annually are given radiotherapy. MATERIALS/METHODS: The Pediatric Radiation Oncology Working Group (APRO) of the German Society for Radiation Oncology (DEGRO) represents the organizational link between GPOH and DEGRO. Their activities range from phrasing guidelines of radio-oncological therapy, through writing a protocol for a prospective study on radiation-induced late effects (RISK--in co-operation with GPOH, 695 patients registered so far) and organizing meetings for information transfer, to implementing radio-oncology within the prospective studies of the GPOH by establishing study chairs for radio-oncology when radio-oncological questions are a primary focus and/or to function as a reference institution for quality assurance. These activities also include individual case consultations outside the study proper. Twice annually the members of the APRO meet for an update on current knowledge and future directions where a representative of the GPOH is invited to contribute special aspects of pediatric oncology. CONCLUSIONS: In the future, modern technology (intensity modulated radiotherapy, proton therapy, inclusion of imaging in treatment planning) will be part of disease management in pediatric oncology. A working group for modern radiotherapy technology was established to enhance this development. Prospective studies of the GPOH with primary or secondary radio-oncological questions require the implementation of corresponding tasks (documentation, monitoring, etc.) in order to meet future demands on clinical trials and to achieve the aims of the protocol. Consequently adequate financial support is indispensable.

Preliminary results of the multicenter trial GPOH-HD 95 for the treatment of Hodgkin's disease in children and adolescents: analysis and outlook.

BACKGROUND: In 5 consecutive pediatric and adolescent Hodgkin's disease trials DAL-HD since 1978 the invasive diagnostic procedures and the radiotherapy have gradually been reduced and chemotherapy modified to minimize toxicity and the risk of late effects. Since 1982 the overall survival increased up to 95%. In this trial the possibility of reducing local radiation doses to 20 Gy in patients with good response to chemotherapy and omitting radiotherapy totally for patients with complete remission after chemotherapy was tested. PATIENTS AND METHODS: Over a period of 6 years, from August 1995 to July 2001, 1018 children and adolescents with Hodgkin's disease from Germany, Austria,Switzerland, the Netherlands, Sweden, Norway and Denmark were enrolled in this trial. The chemotherapy was equivalent to previous trial DAL-HD 90. The treatment group (TG) 1 (stages I and IIA) received 2 cycles OPPA for girls and 2 cycles OEPA for boys, TG2 (stages IIEA, IIB, IIIA) and TG3 (stages IIEB, IIIEA, IIIB, IV) received additional 2 or 4 cycles COPP respectively. In contrast to trial DAL-HD 90 boys in stage IIIB and IIIEB received OPPA instead of OEPA. The initial staging as well as the restaging for evaluating tumor volume reduction after chemotherapy was reviewed by the study center. Radiotherapy was planned accordingly: patients with complete remission after chemotherapy were not irradiated (21.9%); all other patients received local radiotherapy to the initially involved sites, depending on the tu-mor response. Patients with a partial remission of> 75 tumor regression were irradiated with 20 Gy (50AX), partial remission of< 75% with 30 Gy (4.1 %), and residual masses of > 50 ml were boosted up to 35 Gy (20.2 %). RESULTS: 36 tumor progressions and 49 relapses occurred over a period of 7 1/2 years (median followup 3 years, data deadline 12/19/02). Kaplan-Meier-analysis after 5 years showed a probability for event-free survival (pEFS) for all patients of 0.88 and for overall survival (pOS) of 0.97. For the total group the pDFS (disease free survival) was lower in 222 non irradiated patients than in the 758 irradiated patients (0.88 vs. 0.92,p - 0.049). But there was a difference between the individual treatment groups. In TG 1 there was no difference between nonirradiated and irradiated patients (0.97 vs. 0.94) and the non-ir-radiated patients showed a better trend. In TG 2, and in TG 2 and TG 3 combined, the pDFS was significantly worse for non irradiated patients in comparison with the irradiated patients (TG2:0.78 vs. 0.92; TG 2 +3:0.79 vs. 0.91). Compared to former DAL-HD trials the pOS stayed stable despite therapy reduction. CONCLUSIONS: A reduction of radiotherapy to 20 Gy for patients in all stages with good response to chemotherapy is possible without deterioration of the results. The omission of radiotherapy for patients in complete remission after chemotherapy is recommended only for patients in early stages (TG1). In future trials the possibility of a wider selection for chemotherapy alone for this group needs to be evaluated. In intermediate (TG2) and advanced (TG3) stages omission of radiotherapy for patients incomplete remission results in a lower pEFS, but the pOS is not significantly reduced. Only with knowledge of the long term effects of today's therapy we can give a satisfactory answer to the question whether in future trials the primary aim should be pEFS as high as possible due to front-line-therapy or reduction of late effects.

[Validity of diagnoses of mental disorders by primary care physicians]. / Validität von Krankenscheindiagnosen psychischer Störungen.

BACKGROUND AND OBJECTIVE: Even in young adult age, psychological disorders are highly prevalent. Family doctors and gynaecologists are the physicians most often consulted by young women. Hence, they have a special responsibility to diagnose psychiatric disorders and--if necessary--to refer to a specialist. PATIENTS AND METHODS: In a prospective epidemiological study, 342 young women (between 18 and 25 years of age) were questioned two times with a structured interview (F-DIPS) designed for mental disorders. In the time period (1997 and 1998), we also investigated, by analysing personal health insurance data, primary-care physicians' diagnoses and payments for services rendered. The diagnoses were compared. RESULTS: There was only a small accordance between F-DIPS and claimcards. Ambulant treating doctors diagnosed somatoform disorders in 28 % of the young women (F-DIPS: 3, 8 %). The F- DIPS found mostly phobic disorders (29 %) (claimcards: 6,1 %). A disorder-specific therapy was only rarely initiated. The treatment (psychotherapy and/or drug therapy) of women with psychiatric disorders appeared to be insufficient. CONCLUSION: The study indicates that primary-care physicians should be urgently trained in psychiatric diagnostics und therapy.

[4199 biopsies from the endoscopic normal lower duodenum]. / Histologische Befunde bei 4199 Biopsien aus endoskopisch unauffälliger Schleimhaut im tiefen Duodenum.

Lower duodenal biopsies (LDB) are not taken at every oesophago-gastro-duodenoscopy (EGD). In the present study, biopsies from the endoscopic normal lower duodenum were checked as a measure of quality assurance. From 1996 to 2000, 9,955 EGD were performed and 4,199 LDB were taken (42.2 %). Of these, 667 showed pathological histology (15.9 %). A non-specific inflammation was seen in 537 cases and lymphangiectasia in 30 cases. Signs of indigenous sprue were described histologically in 6 LDB. In 4 of the 6 first diagnoses, the LDB was taken owing to clinical suspicion of malabsorption syndrome. Giardia lamblia could be detected in 22 patients. Only 6 of the 22 patients had diarrhoea. A total of 18 clinically relevant first diagnoses were made by LDB in asymptomatic patients with normal endoscopic findings in the duodenum. In order to make a relevant first diagnosis, 233 LDB had to be taken. LDB can be dispensed within EGD when there is neither diarrhoea nor loss of weight, and no anemia, iron deficiency, vitamin deficiency, macrocytosis, hypoproteinaemia, meteorism, joint symptoms or fever.

Response-adapted radiotherapy in the treatment of pediatric Hodgkin's disease: an interim report at 5 years of the German GPOH-HD 95 trial.

PURPOSE: A multinational trial on pediatric Hodgkin's disease (HD) with the aim to reduce the risk of long-term toxicity of combined modality treatment by restricting dose and volume of radiation therapy (RT) while maintaining the excellent treatment results of previous German multicenter trials (DAL-HD82-90). METHODS AND MATERIALS: Patients were treated according to stage of disease (CS) and defined risk factors in three treatment groups (TG) with 2, 4, or 6 cycles of combination chemotherapy. When a complete remission (CR) had been achieved, treatment was terminated without RT independent of initial stage or tumor bulk. Patients with a partial remission (PR) of >75% tumor regression were irradiated with 20 Gy using modified involved fields; in the case of PR <75% RT dose was 30 Gy, residual masses >50 mL received 35 Gy. RESULTS: From August 1995 to July 2000 a total of 956 patients have been registered, 830 as trial patients, 39% in TG1, 27% in TG2, 34% in TG3. 827 patients were evaluable by June 2001 with a median follow-up of 38 months. Chemotherapy (CTx) resulted in CR in 22%, PR >75% in 62%, PR <75% in 12%. Event-free survival (EFS) for the entire group is 90% (SD 0.01), for TG1 94%, TG2 91%, and TG3 84%; the overall survival is 97% in Kaplan-Meier-analysis. Relapse-free survival (RFS) is superior for patients with RT after PR (93%) than for those without RT after CR (89%); the difference is significant (p = 0.01) for advanced stages, however not in TG1. Seventy-two events were observed by June 2001: 28 progressions during the initial therapy or within the first 3 months, 38 relapses, 3 second malignancies, three fatal accidents or infections; 18 patients have died. CONCLUSION: Treatment results of the GPOH-HD 95 trial are excellent thus far. The reduction of RT dose and volume in PR has not caused a significant impairment of overall and event-free survival in comparison to the previous German trials; however, failure rates are higher in advanced stages when RT is omitted after achieving a CR. It is too early to tell whether the HD 95 protocol will be successful in reducing late toxicity.

[Enteropathy-associated T-cell lymphoma. Manifestation as diet-refractory coeliac disease and ulcerating jejunitis]. / Das Enteropathie-assoziierte T-Zell-Lymphom (EATCL). Manifestation als diätrefraktäre Sprue und ulzerierende Jejunitis.

HISTORY AND CLINICAL FINDINGS: A 61-year-old woman in poor general health was admitted to hospital because of progressive diarrheo, flatulence, fatigue and weight loss. The patient had a history of coeliac disease with poor dietary compliance over many years. Hence, the present clinical deterioration was unresponsive to a gluten-free diet. INVESTIGATIONS: Laboratory results showed signs of inflammation and malabsorption. The endoscopy of the duodenum revealed a flattened mucosal architecture, as is typical for coeliac disease. Enteroscopy revealed many small jejunal lesions. Histological examination of mucosa showed typical signs of coeliac disease without definite signs of lymphoma. Immunhistochemical analysis showed atypical intraepithelial T-cells, while the molecular biological study revealed a monoclonal T-cell clone, both supporting the diagnosis of an enteropathy associated T-cell lymphoma (EATCL). DIAGNOSIS AND THERAPY: The patient was enrolled in a study on intestinal non-Hodgkin lymphomas and accordingly received 6 courses of CHOP-chemotherapy. Clinical and histological improvement has lasted for over a year. CONCLUSION: Patients with coeliac disease unresponsive to a gluten-free diet or with a deteriorating clinical condition may have an enteropathy-associated T-cell lymphoma. This can manifest itself in the form of an ulcerative jejunitis. In the early stages of disease, immunhistochemical and molecularbiological analyses may lead to the correct diagnosis.

Low-dose radiation is sufficient for the noninvolved extended-field treatment in favorable early-stage Hodgkin's disease: long-term results of a randomized trial of radiotherapy alone.

PURPOSE: To show that radiotherapy (RT) dose to the noninvolved extended field (EF) can be reduced without loss of efficacy in patients with early-stage Hodgkin's disease (HD). PATIENTS AND METHODS: During 1988 to 1994, pathologically staged patients with stage I or II disease who were without risk factors (large mediastinal mass, extranodal lesions, massive splenic disease, elevated erythrocyte sedimentation rate, or three or more involved areas) were recruited from various centers. All patients received 40 Gy total fractionated dose to the involved field areas but were randomly assigned to receive either 40 Gy (arm A) or 30 Gy (arm B) total fractionated dose for the clinically noninvolved EF. No chemotherapy was given. RT films were prospectively reviewed for protocol violations and recurrences retrospectively related to the applied RT. RESULTS: Of 382 recruited patients, 376 were eligible for randomized comparison, 190 in arm A and 186 in arm B. Complete remission was attained in 98% of patients in each arm. With a median follow-up of 86 months, 7-year relapse-free survival (RFS) rates were 78% (arm A) and 83% (arm B) (P =.093). The upper 95% confidence limit for the possible inferiority of arm B in RFS was 4%. Corresponding overall survival rates were 91% (arm A) and 96% (arm B) (P =.16). The most common causes of death (n = 27) were cardiorespiratory disease/pulmonary embolisms (seven), second malignancy (six), and HD (five). Protocol violation was associated with significantly poorer RFS. Nonirradiated nodes were involved in 42 of 52 reviewed relapses, infield areas in 18, marginal areas in 17, and extranodal sites in 16. CONCLUSION: EF-RT alone attains good survival rates in favorable early-stage HD. The 30-Gy dose is adequate for clinically noninvolved areas. Protocol violation worsens the subsequent prognosis. Relapse patterns suggest that systemic therapy can reduce the 20% long-term relapse rate.

[Ulcerative ileocolitis induced by NSAID therapy]. / Ulzerierende Ileokolitis unter NSAR-Therapie.

HISTORY AND PHYSICAL EXAMINATION: A 67-year-old woman was admitted to our hospital for spasmodic abdominal pain, diarrhea, and general weakness. She had lost 5 kg of weight over the past few weeks. The patient had a 20-year history of chronic analgetic abuse, mainly consuming over-the-counter nonsteroidal anti-inflammatory drugs (NSAID). EXAMINATION: Laboratory examination was remarkable for a low serum albumin (2.3 g/dl), an increased erythrocyte sedimentation rate of 70 mm/h, and a profound anemia of 8.5 g/dl. Ultrasound of the abdomen showed thickening of the colonic wall and distended colon loops filled with fluid. On colonoscopy several ulcerations from the sigmoid to the ileum were seen. Histologic examination showed a nonspecific ileocolitis. DIAGNOSIS, THERAPY AND CLINICAL COURSE: After cessation of NSAID intake diarrhea stopped within a few days. Abdominal pain resolved, anemia improved and the patient gained weight. A second colonoscopy revealed healing of the colonic ulcerations. Additional examinations regarding differential diagnoses showed no pathological results. Clinical course and subsequent clinical and endoscopic controls revealing further improvement confirmed the diagnosis of an NSAID-induced ileocolitis. CONCLUSION: This patient is a typical example for NSAID-induced colonic ulcerations. It should be recognized that NSAID induce ulcers not only in the upper gastrointestinal tract. A careful drug history may provide the clue for the cause of lower gastrointestinal tract ulcerations.

[Anal gland carcinoma with osteoblastic metastases]. / Analdrüsenkarzinom mit osteoblasticher Metastasierung.

HISTORY AND CLINICALLY FINDINGS: A 52-year-old woman was admitted because of anal pain of 6 weeks duration. Physical examination was unremarkable except for a cherry-sized swelling, painful to pressure, on rectal examination. As the erythrocyte sedimentation rate and C-reactive protein were increased (69/115 and 12.1 mg/dl, respectively) and abscess was diagnosed. Carcinoembryonic antigen was within normal limits. INVESTIGATIONS: At rectoscopy a fluctuating abscess-linked swelling was found at 3 cm and a submucous tumour at 5 cm from the anus. TREATMENT AND COURSE: The abscess was cut open and at the level of the dentate line a submucous adenocarcinoma about 3 cm in diameter was resected. A small residual tumour was removed by abdomino-perineal rectal extirpation. As histologically it was an adenocarcinoma not of colorectal type, without relationship to rectal mucosa but in close contact to the anal glands, and the further course did not indicate a metastasis from another primary tumour, the diagnosis of anal gland adenocarcinoma was established. A local recurrency was resected 6 months later, followed by combined radio- and chemotherapy. A diffuse osteoblastic metastasis was discovered later and the patient died 21 months after diagnosis. CONCLUSION: An osteoblastic metastasis from an anal gland carcinoma, as occurred in this case, has not been previously reported.

[Multi-national therapy study for Hodgkin's disease in children and adolescents GPOH-DH 95. Interim report after 2 1/2 years]. / Multinationale Therapiestudie für den Morbus Hodgkin bei Kindern und Jugendlichen GPOH-HD 95. Zwischenbericht nach 2 1/2 Jahren.

Based on concepts of the successful German-Austrian pediatric Hodgkin studies DAL-HD 78 until-90, a new trial was initiated addressing the question whether radiotherapy can be further reduced or can be omitted in case of complete remission after initial chemotherapy, aiming at reduction of sequelae after radiotherapy, especially radiogenic second malignancies. In respect to CHEMOTHERAPY patients are stratified into 3 therapy groups (TG) according to stage and gender: 2 courses of OPPA (girls) or OEPA (boys) in TG1 (stage IA/B, IIA), and in addition 2 (TG2: stage IEA/B, IIEA, IIB, IIIA) or 4 (TG3: stage IIEB, IIIEA/B, IIIB, IVA/B) COPP courses. Boys with stage IIIB and IIIEB receive OPPA instead of OEPA. RADIOTHERAPY is administered according to response to chemotherapy independent of stage: patients with complete remission or minimal residues do not receive irradiation; patients with more than 75% tumor regression are irradiated to involved fields at a dose of 20 Gy. Doses of 30 or 35 Gy are given to regions with tumor regression below 75% or residual bulky tumor of > 50 ml, respectively. INTERIM RESULTS: From 8/95 till 1/98 we registered 385 patients under the age of 18 years from Germany, Austria, Switzerland, Sweden and the Netherlands. Therapy has been completed in 334 patients. Three patients with solitary nodular paragranuloma were treated with surgery only. Out of 331 patients 89 (26.9%) achieved a complete remission with chemotherapy. Tumor regression of more than 75% was seen in 193 (58.3%) patients and below 75% in 39 (11.8%) patients. Tumor progression during chemotherapy occurred in 1 (0.3%) patient. Response after chemotherapy was not evaluable for 9 (2.7%) patients. Radiotherapy was omitted in 91 (27.1%) patients: in TG1 50 of 142 (34%) patients, TG2 24 of 98 (24.5%) patients and TG3 18 of 94 (19.2%) patients. Initially involved regions were irradiated at a dose of 20 Gy in 164 of 334 (49.1%) patients. Doses up to 30 Gy or 35 Gy were given to 19 (5.7%) or 57 (17.1%) patients respectively. Events (tumor progression, relapse or death) occurred in 23 of 334 patients until now. The event-free survival rate is 0.91 at 2 1/2 years for all study patients and 0.89 for patients without radiotherapy. Six relapses occurred in 91 patients without radiotherapy. No relapse occurred in TG1 (n = 49), but in 5 of 24 TG2-patients, and in 1 of 18 TG3 patients without radiotherapy. As yet, the results are not significantly inferior compared with trial DAL-HD 82. Therefore this trial aiming at omitting radiation therapy in patients with complete remission after a short lasting chemotherapy will be continued. Longer follow up is necessary for final evaluations and conclusions.

Dose-response relationship of complementary radiotherapy following four cycles of combination chemotherapy in intermediate-stage Hodgkin's disease.

PURPOSE: To determine the appropriate irradiation dose after four cycles of modern combination chemotherapy in nonbulky involved field (IF/BF) and noninvolved extended-field (EF/IF) sites in patients with intermediate-stage Hodgkin's disease (HD). MATERIALS AND METHODS: HD patients in stage I to IIIA with a large mediastinal mass, E stage, or massive spleen involvement were treated with two double cycles of alternating cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by EF irradiation in two successive trials (HD1 and HD5). In the HD1 trial (1983 to 1988), 146 patients who responded to chemotherapy were randomized to receive 20 Gy (70 patients) or 40 Gy (76 patients) of EF irradiation in all fields outside bulky disease sites. A cohort of 111 patients who fulfilled the same inclusion criteria in the subsequent trial HD5 (1988 to 1993) were treated with 30 Gy. Bulky disease always received 40 Gy. RESULTS: Freedom-from-treatment-failure (FFTF) and survival (SV) curves showed no differences between the 20-, 30-, and 40-Gy groups. However, acute toxicities were more frequent in the 40-Gy arm. Analysis of relapse patterns showed that 18 of 26 relapsing patients either failed to respond in initial bulky sites (n = 5) or had an extranodal relapse (n = 9) or both (n = 4). After 5 years, the cumulative risk for relapse in bulky sites is 10%, despite 40 Gy of radiation. CONCLUSION: Our results strongly suggest that there is no relevant radiotherapy dose effect in the range between 20 Gy and 40 Gy in IF/BF and EF/IF after 4 months of modern polychemotherapy in patients with intermediate-stage HD. Relapse patterns indicate that patients destined to relapse need more systemic, rather than local, treatment. Based on our data, we conclude that 20 Gy is sufficient in EF/IF of intermediate-stage HD following four cycles of modern polychemotherapy.

[Paranasal sinus mycetoma with orbital involvement in a patient with AIDS]. / Nasennebenhöhlenmyzetom mit Einbruch in die Orbita bei einem Patienten mit AIDS.

A patient with AIDS was hospitalized with a left-sided face swelling and protrusion of the bulbus. After cranial computed tomography and fine-needle aspiration biopsy of the fossa temporalis we diagnosed a mycetoma; localisation and histology made an aspergilloma most probable. Antimycotic therapy led to complete remission of the symptoms. Post mortem we only could culture Candida albicans out of the abscess cavity.

Characterization of bile ducts in primary biliary cirrhosis and other liver diseases by immunohistochemical demonstration of Lewis(a) or b antigen.

We investigated Lewis(a) and Lewis(b) expression of bile ducts in 68 specimens from various kinds of liver disease. In addition, the number of IgM and IgG synthesizing plasma cells in the hepatic inflammatory reactions were immunostained and counted. We found a statistically significant decrease in the number of bile ducts in PBC (primary biliary cirrhosis) in comparison with either chronic active or persistent hepatitis (CAH/CPH). Bile ducts could be detected easily and constantly by their Lewis antigen expression. Isolated bile duct epithelial cells not apparent in H&E sections could be identified by Lewis(a) and b immunostaining. The number of plasma cells in PBC was significantly different than in (CAH/CPH). A large number of IgM plasma cells was a characteristic feature of PBC. However, neither counting of Lewis(a) and b positive bile ducts nor counting of IgM plasma cells was of definite diagnostic significance in the individual clinical case, since no cut-off value could be determined above or below which a PBC was ruled out or proven.

[The prognostic factors following the simultaneous radiochemotherapy of anal canal carcinoma in a multicenter series of 139 patients]. / Prognostische Faktoren nach simultaner Radiochemotherapie des Analkanalkarzinoms in einer multizentrischen Serie von 139 Patienten.

PURPOSE: Evaluation of prognostic variables, results and toxicity after chemo-radiation (CRT) of anal canal carcinoma (ACC). MATERIAL AND METHODS: Between 1982 and 1992, 139 patients with epidermoid carcinoma of the anal canal were treated by radiation and chemotherapy with 5-fluorouracil (5-Fu) and mitomycin C (MMC). 99 patients belonged to a prospectively designed trial (50 Gy, 2 courses of chemotherapy) and 40 to a historical control group (40 Gy, 1 course of chemotherapy). The female/male ratio was 116/23. Median age was 62 years. Staging (UICC 1987): T1: 16.5%; T2: 49%; T3: 23%; T4: 9.4%; unknown: 2.1%. Abnormal regional nodes were present in 15% of the patients. HISTOLOGY: Squamous cell carcinoma: 68%; cloacogenic carcinoma: 31%; unknown: 1%. External beam radiation (ERT) was given to the primary tumour including perirectal, inguinal and iliac nodes by a 3 to 4 field box technique (50 patients) or parallel opposed fields (89 patients). Median single fraction and total dose were 1.8 Gy and 50 Gy. An additional boost to the involved sites was delivered by ERT (32 cases; median dose 16 Gy) or interstitial brachytherapy (BT) in 28 cases with a median dose 14 Gy. 84 patients (60%) received 2 or more cycles, 50 patients (36%) 1 cycle, 5 patients (4%) no chemotherapy. RESULTS: The survival rate, NED-survival rate and local tumour control rate were 78%, 64% and 69% at 5 years. Anorectal function was retained in 94 of 139 patients (68%). Multivariate analysis indicated that T-stage (p = 0.037) and belonging to the historical control group (p = 0.003) were significant variables for local tumour control. T-stage was a marginally significant factor (p = 0.09) for NED-survival. Acute toxicity of grade 3 and 4 (WHO) was observed in 36%, severe late toxicity (grade 3 Eschwege) in 3% of the patients. CONCLUSIONS: CRT with 2 courses 5-FU, MMC and ERT to a total dose of 45 to 50 Gy is a safe and effective treatment for ACC. Intensification of treatment is recommended in advanced stages T3/4.

Prognosis of high dose chemotherapy/autologous bone marrow transplantation candidates not receiving this treatment after failure of primary therapy of Hodgkin's disease.

In a multicenter study on the therapy of Hodgkin's disease, in 88 out of 297 patients with primary advanced stages IIIB/IV, a failure to the treatment with the alternating chemotherapy COPP/ABVD +/- radiation was recorded. The cause of failure was as follows: tumor progression under current therapy (PD) 23/88, partial response at the end of therapy (PR) 28/88, early nodal relapses 13/88, late nodal relapses 16/88, extranodal relapses 7/88, undetermined localization 1/88.36 months after manifestation of the failure to treatment, 45% of all patients were still alive. In cases of primary PD the prognosis was the worst of all. Only 1/23 of these patients received a long-term continuous complete remission (cCR) with the salvage therapy. 11 patients with only a nodal relapse received a cCR with irradiation alone. These cases could be regarded as low risk relapses. For the high risk relapse group (n = 57) an indication for high dose chemotherapy with subsequent autologous bone marrow transplantation (HDC/ABMT) would have been imperative, following the present-day definition. The probability of survival of these patients who, however, only received a conventional salvage therapy was up to 38% (95% confidence interval 22-54%). Comparing these data with the literature our results seem not to be substantially worse than those for patients who underwent HDC/ABMT. Only in a randomized comparison can the decision be made on whether HDC/ABMT would be superior to high dose conventional chemotherapy supported by hematopoietic growth factors. It is suggested that such a therapy study be performed as soon as possible.

[Correlation between pulmonary hypertension and portal hypertension--2 case reports of different forms of pre-sinusoidal portal hypertension]. / Zum Zusammenhang zwischen pulmonaler Hypertonie und portaler Hypertension--zwei Kasuistiken von unterschiedlichen Formen von präsinusoidaler portaler Hypertension.

Since its first description in 1951 by Mantz and Craig pulmonary hypertension in combination with portal hypertension has been observed more and more frequently. In a recent prospective study Hadengue et al. reported an incidence of 2%. Thus this simultaneous occurrence can no longer be considered to be coincidental. The etiology remains still unclear. It is most probable that the development is due to vasoactive substances which bypass the liver or which are produced in the lung itself, and which, due to a long-term vasoconstriction, causes irreparable damage to the arterioles and arteries in the lung. Such pulmonary hypertension can develop in the presence of a pre- as well as an intrahepatic block, even when the portal hypertension is partially or completely alleviated by a portosystemic anastomosis. This last circumstance can be illustrated by two cases which were observed by our group. Case A is of particular interest because it is the first documentation of a case of an intrahepatic block due to a (so-called) macronodular transformation of the liver in the absence of portal thrombosis (a so-called NRH: nodular regenerative hyperplasia) in combination with pulmonary hypertension. This type of non-cirrhotic portal hypertension can be associated with micronodular transformation of the liver as well. Post-hepatic blocks or the so-called BUDD-CHIARI Syndrome type appear to carry no risk of development of pulmonary hypertension. It remains unclear which particular etiologies increase susceptibility to later development of pulmonary hypertension.